ID C1GLT_HUMAN Reviewed; 363 AA. AC Q9NS00; Q96QH4; Q9BTU1; DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 154. DE RecName: Full=Glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1; DE EC=2.4.1.122 {ECO:0000269|PubMed:11677243}; DE AltName: Full=B3Gal-T8; DE AltName: Full=Core 1 O-glycan T-synthase; DE AltName: Full=Core 1 UDP-galactose:N-acetylgalactosamine-alpha-R beta 1,3-galactosyltransferase 1; DE Short=Beta-1,3-galactosyltransferase; DE AltName: Full=Core 1 beta1,3-galactosyltransferase 1; DE Short=C1GalT1; DE Short=Core 1 beta3-Gal-T1; GN Name=C1GALT1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP PATHWAY, AND TISSUE SPECIFICITY. RX PubMed=11677243; DOI=10.1074/jbc.m109060200; RA Ju T., Brewer K., D'Souza A., Cummings R.D., Canfield W.M.; RT "Cloning and expression of human core 1 beta1,3-galactosyltransferase."; RL J. Biol. Chem. 277:178-186(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RA Jensen M.P.A.; RT "Cloning and expression of a novel beta-1,3-galactosyltransferase."; RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 79-363 (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP INTERACTION WITH C1GALT1C1. RX PubMed=12464682; DOI=10.1073/pnas.262438199; RA Ju T., Cummings R.D.; RT "A unique molecular chaperone Cosmc required for activity of the mammalian RT core 1 beta 3-galactosyltransferase."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16613-16618(2002). RN [7] RP MUTAGENESIS OF ARG-140; TYR-201; TYR-206; ASP-240; TRP-285 AND TYR-310. RX PubMed=35504880; DOI=10.1038/s41467-022-29833-0; RA Gonzalez-Ramirez A.M., Grosso A.S., Yang Z., Companon I., Coelho H., RA Narimatsu Y., Clausen H., Marcelo F., Corzana F., Hurtado-Guerrero R.; RT "Structural basis for the synthesis of the core 1 structure by C1GalT1."; RL Nat. Commun. 13:2398-2398(2022). RN [8] RP INVOLVEMENT IN IGA NEPHROPATHY. RX PubMed=17228361; DOI=10.1038/sj.ki.5002088; RA Li G.-S., Zhang H., Lv J.-C., Shen Y., Wang H.-Y.; RT "Variants of C1GALT1 gene are associated with the genetic susceptibility to RT IgA nephropathy."; RL Kidney Int. 71:448-453(2007). RN [9] RP INVOLVEMENT IN IGA NEPHROPATHY. RX PubMed=19357720; DOI=10.1038/ki.2009.99; RA Zhu L., Tang W., Li G., Lv J., Ding J., Yu L., Zhao M., Li Y., Zhang X., RA Shen Y., Zhang H., Wang H.; RT "Interaction between variants of two glycosyltransferase genes in IgA RT nephropathy."; RL Kidney Int. 76:190-198(2009). CC -!- FUNCTION: Glycosyltransferase that generates the core 1 O-glycan Gal- CC beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many CC extended O-glycans in glycoproteins (PubMed:11677243). Plays a central CC role in many processes, such as angiogenesis, thrombopoiesis and kidney CC homeostasis development (By similarity). {ECO:0000250|UniProtKB:Q9JJ06, CC ECO:0000269|PubMed:11677243}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an N-acetyl-alpha-D-galactosaminyl derivative + UDP-alpha-D- CC galactose = a beta-D-galactosyl-(1->3)-N-acetyl-alpha-D- CC galactosaminyl derivative + H(+) + UDP; Xref=Rhea:RHEA:15621, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28257, ChEBI:CHEBI:58223, CC ChEBI:CHEBI:66914, ChEBI:CHEBI:133470; EC=2.4.1.122; CC Evidence={ECO:0000269|PubMed:11677243}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:Q9JJ05}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:11677243}. CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with CC the C1GALT1C1 chaperone; required for galactosyltransferase activity CC (PubMed:12464682). {ECO:0000250|UniProtKB:Q9JJ05, CC ECO:0000269|PubMed:12464682}. CC -!- INTERACTION: CC Q9NS00; Q96EU7: C1GALT1C1; NbExp=4; IntAct=EBI-8628584, EBI-2837343; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9JJ05}; Single- CC pass type II membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NS00-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NS00-2; Sequence=VSP_024809; CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in kidney, CC heart, placenta and liver. {ECO:0000269|PubMed:11677243}. CC -!- MISCELLANEOUS: Aberrant O-galactosylation of IgA1 molecules plays a CC role in the development and progression of IgA nephropathy (IgAN). CC Genetic interactions of C1GALT1 and ST6GALNAC2 variants influence IgA1 CC O-glycosylation, disease predisposition, and disease severity, and may CC contribute to the polygenic nature of IgAN. CC -!- SIMILARITY: Belongs to the glycosyltransferase 31 family. Beta3-Gal-T CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=Core1 CC UDP-galactose:N-acetylgalactosamine-alpha-R beta CC 1,3-galactosyltransferase; CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_447"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF155582; AAF81981.1; -; mRNA. DR EMBL; AJ132443; CAC45046.1; -; mRNA. DR EMBL; AJ278960; CAC82373.1; -; mRNA. DR EMBL; AJ243256; CAC80435.1; -; mRNA. DR EMBL; AC005532; AAQ96887.1; -; Genomic_DNA. DR EMBL; CH236948; EAL24308.1; -; Genomic_DNA. DR EMBL; BC003174; AAH03174.1; -; mRNA. DR CCDS; CCDS5355.1; -. [Q9NS00-1] DR RefSeq; NP_064541.1; NM_020156.4. [Q9NS00-1] DR RefSeq; XP_011513755.1; XM_011515453.2. DR RefSeq; XP_011513757.1; XM_011515455.2. DR RefSeq; XP_011513758.1; XM_011515456.2. [Q9NS00-1] DR RefSeq; XP_016867931.1; XM_017012442.1. [Q9NS00-1] DR RefSeq; XP_016867932.1; XM_017012443.1. DR RefSeq; XP_016867933.1; XM_017012444.1. [Q9NS00-1] DR RefSeq; XP_016867934.1; XM_017012445.1. [Q9NS00-1] DR RefSeq; XP_016867935.1; XM_017012446.1. DR RefSeq; XP_016867936.1; XM_017012447.1. DR RefSeq; XP_016867937.1; XM_017012448.1. [Q9NS00-1] DR AlphaFoldDB; Q9NS00; -. DR SMR; Q9NS00; -. DR BioGRID; 121241; 50. DR IntAct; Q9NS00; 7. DR MINT; Q9NS00; -. DR STRING; 9606.ENSP00000389176; -. DR ChEMBL; CHEMBL2321633; -. DR CAZy; GT31; Glycosyltransferase Family 31. DR iPTMnet; Q9NS00; -. DR PhosphoSitePlus; Q9NS00; -. DR BioMuta; C1GALT1; -. DR DMDM; 74719147; -. DR EPD; Q9NS00; -. DR jPOST; Q9NS00; -. DR MassIVE; Q9NS00; -. DR MaxQB; Q9NS00; -. DR PaxDb; 9606-ENSP00000389176; -. DR PeptideAtlas; Q9NS00; -. DR ProteomicsDB; 82459; -. [Q9NS00-1] DR ProteomicsDB; 82460; -. [Q9NS00-2] DR Pumba; Q9NS00; -. DR Antibodypedia; 2308; 167 antibodies from 25 providers. DR DNASU; 56913; -. DR Ensembl; ENST00000223122.4; ENSP00000223122.2; ENSG00000106392.11. [Q9NS00-1] DR Ensembl; ENST00000402468.3; ENSP00000384550.3; ENSG00000106392.11. [Q9NS00-2] DR Ensembl; ENST00000436587.7; ENSP00000389176.2; ENSG00000106392.11. [Q9NS00-1] DR GeneID; 56913; -. DR KEGG; hsa:56913; -. DR MANE-Select; ENST00000436587.7; ENSP00000389176.2; NM_020156.5; NP_064541.1. DR UCSC; uc003sra.5; human. [Q9NS00-1] DR AGR; HGNC:24337; -. DR CTD; 56913; -. DR DisGeNET; 56913; -. DR GeneCards; C1GALT1; -. DR HGNC; HGNC:24337; C1GALT1. DR HPA; ENSG00000106392; Low tissue specificity. DR MIM; 610555; gene. DR neXtProt; NX_Q9NS00; -. DR OpenTargets; ENSG00000106392; -. DR PharmGKB; PA134971259; -. DR VEuPathDB; HostDB:ENSG00000106392; -. DR eggNOG; KOG2246; Eukaryota. DR GeneTree; ENSGT00940000155000; -. DR HOGENOM; CLU_035857_0_0_1; -. DR InParanoid; Q9NS00; -. DR OMA; WLLSKHD; -. DR OrthoDB; 360875at2759; -. DR PhylomeDB; Q9NS00; -. DR TreeFam; TF317293; -. DR BioCyc; MetaCyc:HS02901-MONOMER; -. DR BRENDA; 2.4.1.122; 2681. DR PathwayCommons; Q9NS00; -. DR Reactome; R-HSA-5083632; Defective C1GALT1C1 causes TNPS. DR Reactome; R-HSA-913709; O-linked glycosylation of mucins. DR SignaLink; Q9NS00; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 56913; 19 hits in 1123 CRISPR screens. DR ChiTaRS; C1GALT1; human. DR GenomeRNAi; 56913; -. DR Pharos; Q9NS00; Tbio. DR PRO; PR:Q9NS00; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q9NS00; Protein. DR Bgee; ENSG00000106392; Expressed in amniotic fluid and 189 other cell types or tissues. DR ExpressionAtlas; Q9NS00; baseline and differential. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0016263; F:glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB. DR GO; GO:0060576; P:intestinal epithelial cell development; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IMP:UniProtKB. DR GO; GO:0006493; P:protein O-linked glycosylation; IEA:Ensembl. DR Gene3D; 3.90.550.50; -; 1. DR InterPro; IPR026050; C1GALT1/C1GALT1_chp1. DR InterPro; IPR003378; Fringe-like_glycosylTrfase. DR PANTHER; PTHR23033; BETA1,3-GALACTOSYLTRANSFERASE; 1. DR PANTHER; PTHR23033:SF13; GLYCOPROTEIN-N-ACETYLGALACTOSAMINE 3-BETA-GALACTOSYLTRANSFERASE 1; 1. DR Pfam; PF02434; Fringe; 1. DR Genevisible; Q9NS00; HS. PE 1: Evidence at protein level; KW Alternative splicing; Angiogenesis; Developmental protein; Differentiation; KW Disulfide bond; Glycosyltransferase; Manganese; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Signal-anchor; KW Transferase; Transmembrane; Transmembrane helix. FT CHAIN 1..363 FT /note="Glycoprotein-N-acetylgalactosamine 3-beta- FT galactosyltransferase 1" FT /id="PRO_0000285064" FT TOPO_DOM 1..6 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 7..29 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 30..363 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REGION 41..72 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 94 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 138 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 139 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 140 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 146 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 169 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 169 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 171 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 285 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 309 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 309 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT BINDING 310 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT MOD_RES 235 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JJ06" FT DISULFID 91..115 FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT DISULFID 232..246 FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT DISULFID 300..301 FT /evidence="ECO:0000250|UniProtKB:Q7K237" FT VAR_SEQ 297..363 FT /note="GPGCCSDLAVSFHYVDSTTMYELEYLVYHLRPYGYLYRYQPTLPERILKEIS FT QANKNEDTKVKLGNP -> VSLEILLLCQYLD (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_024809" FT MUTAGEN 140 FT /note="R->A: Reduced activity." FT /evidence="ECO:0000269|PubMed:35504880" FT MUTAGEN 201 FT /note="Y->A: Reduced activity." FT /evidence="ECO:0000269|PubMed:35504880" FT MUTAGEN 206 FT /note="Y->A: Reduced activity." FT /evidence="ECO:0000269|PubMed:35504880" FT MUTAGEN 240 FT /note="D->A: Inactive." FT /evidence="ECO:0000269|PubMed:35504880" FT MUTAGEN 285 FT /note="W->A: Inactive." FT /evidence="ECO:0000269|PubMed:35504880" FT MUTAGEN 310 FT /note="Y->A: Reduced activity." FT /evidence="ECO:0000269|PubMed:35504880" SQ SEQUENCE 363 AA; 42203 MW; 01F472B55C5F526F CRC64; MASKSWLNFL TFLCGSAIGF LLCSQLFSIL LGEKVDTQPN VLHNDPHARH SDDNGQNHLE GQMNFNADSS QHKDENTDIA ENLYQKVRIL CWVMTGPQNL EKKAKHVKAT WAQRCNKVLF MSSEENKDFP AVGLKTKEGR DQLYWKTIKA FQYVHEHYLE DADWFLKADD DTYVILDNLR WLLSKYDPEE PIYFGRRFKP YVKQGYMSGG AGYVLSKEAL KRFVDAFKTD KCTHSSSIED LALGRCMEIM NVEAGDSRDT IGKETFHPFV PEHHLIKGYL PRTFWYWNYN YYPPVEGPGC CSDLAVSFHY VDSTTMYELE YLVYHLRPYG YLYRYQPTLP ERILKEISQA NKNEDTKVKL GNP //